Abstract 1115

A small subset of genes is transcribed during latency in Kaposi sarcoma-associated herpesvirus (KSHV) lymphomas. To better understand viral lymphomagenesis we generated a transgenic mouse expressing all viral latent genes including LANA, vFLIP, vCyc, kaposin and all viral miRNAs. All viral miRNAs were expressed in B cells. The complete latency locus induced activation of mature B cells more robustly than a single LANA protein transgenic mouse. It led to the specific expansion of marginal zone (MZ) B cells. The transgenic mice showed an augmented primary response to T-dependent antigen leading to acute MZ activation and germinal center (GC) activation. Furthermore, they exhibited an augmented response to TLR4 stimulation. Our data indicates that the KSHV latency locus fuels transformation processes as a chronic antigenic stimulator. These data supports a model of lymphomagenesis, in which virally infected B cells become hyperresponsive to B cell stimulation, thus providing an expanded pool for secondary genetic alterations.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
antigens, b-lymphocytes, human herpesvirus 8, leukemogenesis, lymphoma, micrornas, toll-like receptor 4, mice, transgenic, germinal center of lymph node, genes

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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